Eradicating HMRV (or whatever they name it next)

>Over time, the infections of various organs tended to be cleared by either immune mechanisms but especially by restriction enzyme systems present in almost all human cells that hypermutate the virus so it cannot persist as a competent infectious agent.

Best, Lisa

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I was confused by this statement. Because it leads you to believe that the virus is completely cleared eventually. But then he goes on to say later that even though they thought it was cleared, it came roaring back upon injection of an immune stimulant.

"Perhaps most interesting of all was what happened with the injection of a bolus of foreign peptides into macaques that had apparently completely cleared the virus from blood. There was a huge reactivation of infectious virus in the blood proving that latent but persistent virus is just below the surface and that XMRV infection cannot be completely cleared from all reservoir sites. The peptide injection mimics an acute infection (? borrelia or the flu), an immunization or even acute mold exposure."

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So I guess the question is... if you can keep away from further immune insults that will increase replication again substantially (ie infection, mold, significant stress (cortisol), androgen spikes, etc..) will the virus eventually completely clear from the organ/tissue reservoirs - or, will it always come roaring back given the right stimulation?

And, is it even possible to set up a situation where the virus won't be stimulated at all? Or a situation where the immune system is clearing it faster via restriction enzymes than it can replicate? Some triggers you can avoid - mold, gluten, allergies (for the most part), infections (sort of), but cortisol you can't live without, and androgens not really either.

Maybe with ARVs, it will prevent replication upon being provoked by those factors so that eventually the body can clear the infection. The question is how long would that take. They thought the same would happen in HIV, since T-cells (the main reservoir for HIV - or so was thought at the time) turn over pretty quickly. But then they discovered places where HIV hides (resting T-cells, longer lived tissues) that would take decades to cycle though... making a cure using ARVs unlikely.

Or maybe like was stated above, they can hypermutate the virus faster and clear it from the organs faster using some sort of drug.

m0joy..u might wanna check out my thread on HIV research...i like the Tre Recombinase approach. doing humanized mice trials right now. takes about 3 years to make a recombinase for a new virus. max plank institute. they were able to eradicate i think 80% of virus from a mouse using that alone. snips HIV out of genome. will be ready for human trials in 10-20 years.

XMRV will, i think, be more difficult to eradicate than HIV.

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No one really knows. I dont think it is helpful to dwell on a certain possible treatment for AIDS which could take 10-20 years. New discoveries and completely different treatments arent uncommon and who knows when the next breakthrou in a field may come. Sometimes it just takes one piece of new knowledge to completely change something.

This virus seems to also be quite different to AIDS in many ways, its a brand new thing. We still dont even know if it is a secondly thing in our condition, it may not even be causative to CFS/ME. The answer may still be laying completely elsewhere.

I was thinking about Gcmaf the other day. It would really be baffling to me if it really was able to eradicate HIV given that macrophages are a prime infection reservoir. If it works, logically it must work by immune modulating: enabling enough healthy macrophages to gain an upper hand on the virus. The mixed responses we've heard so far seem to fit the immune modulation theory more than the eradication theory.

I heard from one CFS specialist that was at the conference that he thinks that the envelope protein is the main determining factor of pathology. He is against the use of HAART and says there is no drug at the moment that stops the integrated virus from making more envelope protein.

The same mechanism used to make new copies of viral RNA is used to make the messenger RNA which is translated into envelope proteins.

I was reading that not only HIV itself dynamic but HIV envelope proteins are also dynamic:

"Despite its importance, there are no antiviral drugs that target the envelope protein, in part because the virus is extraordinarily clever at changing the pieces of the protein it presents to the outside world."

Is it safe to assume this may be the case with MLVs as well? So what the doc above seemed to be saying was that instead of using drugs that block the envelope protein which would attach to the host cell, which would require specificity, we should find drugs that stop the churning out of proteins to begin with.

Then we seem to go back to the restriction enzyme systems which work on the proviral DNA right? If you hypermutate the virus or cut it out of the host genome and it can no longer produce RNA or messenger RNA, then neither continual replication of the virus or the envelope protein is an issue in the long-run. In summary, we might be looking at these necessary steps in therapy:

1) prevent cell entry (blocking viral proteins from attaching to host cell or modifying/removing XPR1 receptor depending on its function)
2) prevent viral RNA that has already entered the cell from being transcribed into double-stranded viral DNA (reverse transcriptase inhibitor a la AZT, tenofovir)
3) prevent the newly-transcribed DNA from entering the host genome (integrase inhibitor a la Raltegravir)
4) prevent proviral DNA from being transcribed by cutting it out of the host genome (Tre Recombinase or other restriction enzyme mimicors?)
5) modulate immune system to resolve freely roaming retroviruses post-release from the cell

So I guess the question is... if you can keep away from further immune insults that will increase replication again substantially (ie infection, mold, significant stress (cortisol), androgen spikes, etc..) will the virus eventually completely clear from the organ/tissue reservoirs - or, will it always come roaring back given the right stimulation?

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I wonder what level of stimulation is needed to make it roar back into activation.

Like it's not THAT hard to avoid truly moldy buildings. But this extreme avoidance stuff really sucks.

I'd like to hear how easily it reactivated in the monkeys.

But really....think about it. Most people with ME/CFS report some big combination of stressors prior to getting the illness.

Rarely was it just a bad flu that came out of nowhere. Usually it was more gradual-then-sudden, often preceded by a combination of bad things: a vaccine, a head/neck injury, a WHOLE lot of emotional/physical stress, a trip to Lake Tahoe, living in a really moldy building.

That makes me think that it really doesn't activate that easily. It takes a lot to tip it over the edge.

If I could go back in time to 1994, knowing what I do now, I don't think I'd have gotten permanent ME/CFS. I certainly wouldn't have gotten that vaccine, I'd have had the mold in my house remediated, I wouldn't have taken up ice skating as a hobby, I'd have not gotten pregnant when I already had had other stressful things happen beforehand and my system was lagging. I'd have stayed away from Berkeley (a Lake Tahoe equivalent).

That way, I don't think a bad flu would have knocked me over.

So yeah, I think I'm up for getting this stuff out of the viral reservoirs. I'm pretty sure I could keep it under control permanently if I could just do that.

That's not true in my case and when I first became ill it was an epidemic where many, many people had an acute viral onset from out of the blue. Whatever "tipped us over" was very quick.

When Dr Ramsay and other ME pioneers wrote about ME that was how the majority of their patients reported it. An acute onset on a previously well adult, well one day and then acutely ill the next. That means that the original trigger for ME was very quick. There's a huge amount of history about acute onset viral ME.

I watched a video conference from Dr Mackay (sp) from Stanford university and he mentioned in a Q & A session his thoughts on the guaifensen protocol by
Dr St Amand. He did not really believe in the protocol, but had found some use. I only mention this as he talked about how he felt that the higher doses that people use are not necessary as he found that for some reason I believe 300 mg guaifensen helped glial cells. Basically taking one pill had an effect. Interesting because you mentioned in your brief about this: astrocytes (glial cells in the brain) http://pag.aids2010.org/Abstracts.aspx?AID=6543

I no longer do the protocol, but continue taking the one pill a day hoping that it helps my glial cells. Cheap, no known harm.

That's not true in my case and when I first became ill it was an epidemic where many, many people had an acute viral onset from out of the blue. Whatever "tipped us over" was very quick.

When Dr Ramsay and other ME pioneers wrote about ME that was how the majority of their patients reported it. An acute onset on a previously well adult, well one day and then acutely ill the next. That means that the original trigger for ME was very quick. There's a huge amount of history about acute onset viral ME.

XMRV+

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What I've heard more of is "gradual then sudden": that people showed initial symptoms for a while prior to getting the "killer flu," then were suddenly knocked down into ME/CFS.

But also, I'm positing that the vast majority of ME/CFS patients were exposed to a whole lot of toxic mold in their residences or workplaces for a long time before getting the virus that tipped them over into ME/CFS.

That makes it look like it's just the virus that did the dirty deed, even though there were other factors not showing an effect.

Ditto things like vaccines, which might still be having a subclinical effect for months prior. Or even emotional stress or overwork, which isn't a CAUSE of ME/CFS but conceivably could be a trigger.

Of course, I don't have any proof that most ME/CFS sufferers were living in moldy residences or working in moldy buildings prior to having their XMRV go active. It's just my observation.

m0joey....what you said souds exactly right to me. i also had a top researcher tell me that we might have to find a way to stop Env protein expression, which would be very difficult.

i was hoping that the body's innate immune response might get rid of most of the infected cells on its own, in time, and the ARV's would prevent further spreading. but maybe getting rid of infected cells would take years? i dont know. you mentioned peterson made a comment that this could take years...

that researcher told me that i could hope for that....he seemed to be saying that it might be a reasonable hope.

i did contact the Tre recombinase researchers, who told me it would probably take approx. 3 years to make one for another virus. since the science is still 2 decades away from application to HIV, i didnt ask any further questions about our virus.

i think nanotechnology will be important to get these drugs into the infected cells....

I wanted to comment on mitosis. Like you, I've found that gammaretroviruses replicate mainly, if not solely, during mitosis (cell division), although it's probably safer to assume they can infect actively-dividing and non-dividing cells. Somatic cells (adult stem cells included) and gametes(sex cells) both divide in a process called mitosis. This might suggest that the riskiest time for infection with MLVs is during stem cell division, since that is when cells are dividing the fastest. Non-stem cell somatic cells only divide 20-50 times during their lifetime, but it's exponential for stem cells. This is another reason to hold off on umbilical cord stem cell transplants.

An interesting side note is that this may be why we feel so much worse after overexertion: cells are undergoing mitosis to repair the tissue and being actively infected at the same time.

As for how this changes treatment, it would seem it doesn't really. We still need to take care of proviral DNA in the host genome so it doesn't get replicated during mitosis.

An interesting side note is that this may be why we feel so much worse after overexertion: cells are undergoing mitosis to repair the tissue and being actively infected at the same time.

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I've been aware of the risk of viral reactivation in stem cell transplant (even from one's own bone marrow), but the above is also a very interesting theory, mojoey.

This virus could explain SO much about what goes wrong in us....

For instance I recently started on micro-dose hydrocortisone to try and kick-start my non-functional adrenals, and instantly had viral reactivation (haven't tested for X/P yet, but recognized the EBV/HSV reactivation signs.) I am beginning to suspect that the adrenal shutdown, like so many of our symptoms, is actually a compensation the body makes to keep the viruses under control. It would seem certain systems are down-regulated deliberately by the body in order to lower replication of viral pathogens. This could be an argument that there's no point in treating most of the systemic dysfunctions until XMRV is under control.

leela, I agree, and interestingly that is what Cheney says in one regard, that body shuts down to maintain its version of homeostasis and could explain MCS too as body is saying can't handle more right now, but he was sending people to get stem cells on the other hand. I do not know how he has modified that part of his treatment protocol in light of xmrv (stem cells) if he has?

leela, I agree, and interestingly that is what Cheney says in one regard, that body shuts down to maintain its version of homeostasis and could explain MCS too as body is saying can't handle more right now, but he was sending people to get stem cells on the other hand. I do not know how he has modified that part of his treatment protocol in light of xmrv (stem cells) if he has?

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Does anyone know how he's been dealing with Herpes-family reactivation with stem cell transplant? Perhaps that is not an issue with u-cord cells? (seems like it would be though, what with having to supress the imm sys and all)
I spoke with the office of the doc in Cali who does stem cell transplants from your own bone marrow, but he always sees herpes reactivation with that in carriers, and prescribes Valtrex or what have you for post-procedure. His office also specifically recommends you resolve all issues like HM toxicity, infections, etc before having the bone marrow stem cell treatment. Does anyone know how cheney has been dealing with these issues?

cruzgirl, do you avoid salicylates too? I read about amand stuff like 8-9 years ago and bought some guifanesen but it made me feel way too terrible to use, think bad headache and malaise, was too bad of side fx. I think I remember trying to avoid salicylates and thinking that I figured have some sensitivtiy perhaps to them but it is too hard for me to have ever really given the avoidance of all of them a try.

so, I am in a bit of a state today as just found out am xrmv+ per culture from VIP, took like a couple months to get the results. NOt sure what will do with the info, but think I want to make some plan soon. Lots of layers of things and complications to figure out no matter what but glad to know, mentally, feel like it explains some stuff more firmly in my mind, for my own sake.

so am here trying to look more closely at these sort of threads tonight on what I might want to try to do if anything, and so Joey and daffodil you guys seem to get the science at a much deeper level than I, I dont really know what this means that Joey wrote:

"1) prevent cell entry (blocking viral proteins from attaching to host cell or modifying/removing XPR1 receptor depending on its function)
2) prevent viral RNA that has already entered the cell from being transcribed into double-stranded viral DNA (reverse transcriptase inhibitor a la AZT, tenofovir)
3) prevent the newly-transcribed DNA from entering the host genome (integrase inhibitor a la Raltegravir)
4) prevent proviral DNA from being transcribed by cutting it out of the host genome (Tre Recombinase or other restriction enzyme mimicors?)
5) modulate immune system to resolve freely roaming retroviruses post-release from the cell"

but am curious if you guys or others have an opinion on whether its safe to continue my experiment w/pulsing low dose valtrex, not far into the experiment but when tried to take it regularly last year got way too flared up so taking modified approach now. not sure can deal this year with my dif approach to it which got complicated about 10 days into experiment as emergency root canal came up last week and that isnt good so interrupted what i was doing and worries me cus seem to have gotten some viral reactivation from the dental work been having the last couple weeks.

also curious what you think of just doing an immune modulator without doing the other steps first above. I tried LDN for 6 months couple years ago and there were pros and cons and I think good research on it but I have too much pain that it ultimately couldnt address well enough during a flare so went off it. shortly after the trial of LDN I coincidentally had redlabs cfs panel and still had the cfs biomarkers with rnase and elastase high and natkiller cells low but interestingly my interleukins were normal, I wonder if the LDN helped them or if that was just how I would have tested either way.

For instance I recently started on micro-dose hydrocortisone to try and kick-start my non-functional adrenals, and instantly had viral reactivation (haven't tested for X/P yet, but recognized the EBV/HSV reactivation signs.) I am beginning to suspect that the adrenal shutdown, like so many of our symptoms, is actually a compensation the body makes to keep the viruses under control. It would seem certain systems are down-regulated deliberately by the body in order to lower replication of viral pathogens. This could be an argument that there's no point in treating most of the systemic dysfunctions until XMRV is under control.

That's not true in my case and when I first became ill it was an epidemic where many, many people had an acute viral onset from out of the blue. Whatever "tipped us over" was very quick.

When Dr Ramsay and other ME pioneers wrote about ME that was how the majority of their patients reported it. An acute onset on a previously well adult, well one day and then acutely ill the next. That means that the original trigger for ME was very quick. There's a huge amount of history about acute onset viral ME.

XMRV+

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What if you and the others who ended up with CFS/ME were in that 6% of the community who already carried XMRV ..... and then just on catching something else going around eg a certain viral stressor be it mono or another virus ..... all these ones suddenly developed CFS/ME symptoms.

I still think its possible that XMRV may be there.. laying low.. until a certain stressor comes along. Epidemics dont count that possibily out.

Since cheney is using stem cells primarily to modulate the immune system, this would improve the things you mentioned (in theory) by modulating the immune system. I think he agrees that anti-XMRV strategy both before and after stem cells are important, but he's using artesunate mainly for this, for better or worse. I think once he finds a better alternative, we'll hear about it.

1) prevent cell entry (blocking viral proteins from attaching to host cell or modifying/removing XPR1 receptor depending on its function)
2) prevent viral RNA that has already entered the cell from being transcribed into double-stranded viral DNA (reverse transcriptase inhibitor a la AZT, tenofovir)
3) prevent the newly-transcribed DNA from entering the host genome (integrase inhibitor a la Raltegravir)
4) prevent proviral DNA from being transcribed by cutting it out of the host genome (Tre Recombinase or other restriction enzyme mimicors?)
5) modulate immune system to resolve freely roaming retroviruses post-release from the cell"

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xrayspex--

Those are just some possible treatment considerations based on what we know about the retrovirus' mechanism of infection. Obviously they include the big three that are already being used (azt, tenofovir, raltegravir), but I thought it'd be helpful to illustrate where they fit into the overall picture of the retrovirus lifecycle.

Low dose valtrex shouldn't do much harm; just watch those liver enzymes depending on the dosage.

LDN seems to really help some, but it won't cure a retrovirus obviously.